17alpha-fluoro, 17beta-chlorofluoroacetoxy and 17beta-methyl-5, 10-seco-5, 19-cyclo-androstane derivatives



United States Patent 0 17a-FLUORO, 17 p-CHLOROFLUOROACETOXY AND 17B-METHYL 5,10 SECO-5,19-CYCLO-ANDRO- STANE DERIVATIVES Lawrence H. Knox, Mexico City, Mexico, assignor to Syntex Corporation, Panama, Panama, a corporation of Panama No Drawing. Filed Mar. 19, 1964, Ser. No. 353,240

12 Claims. (Cl. 260-487) The present invention relates to certain novel cyclopentanophenanthrene derivatives and to the method for making the same,

More particularly, the present invention relates to certain novel 17u-fiuoro,17B-chlorofluoroacetoxy and 17B- methyl derivatives of the androstane series, represented by the following formulas:

h a b 3,278,587 Patented Oct. 11, 1966 In practicing the process outlined above, a 3-alkyl, alkenyl or alkinyl substituted derivative of 5,10-seco-5,19- cycle-A -androstatrien-176-016 one (I) obtained by reaction of 5,10-methylene-19-nor-A -androsten-17fi-0l-3- one with a Grignard reagent, as described in my copending application Serial No. 346,096, filed February 20, 1964, is treated with l to 1.5 molar equivalents of a fluorinated amine such as 2-chloro-1,1,2-trifluorotriethylamine in a suitable organic solvent, at a temperature comprised between room temperature and the steam bath for a period of time of between 5 minutes to 3 hours. The solvent is then evaporated under reduced pressure, and the residue chromatographed on neutral alumina, thus producing the corresponding 17a-fluoro- (II) 17fl-chlorofluoroacetoxy- (III) and 17,8-methyl-A (IV) derivatives.

The solvent suitable for the reaction are acetonitrile, ethers such as diethyl ether, isopropyl ether, dioxane, tetrahydrofuran, Dowanol and the like, aromatic hydrocarbons such as benzene, toluene, xylene, etc. In general, the reaction can be carried out in any organic solvent without acidic hydrogen.

Examples of suitable starting materials for the process of the present invention are:

3-methyl-5,lO-seco-S,19-cyclo-A -androstatrien- 3-propinyl-5, 1O-seco-5,19-cyclo-A -androstatrien- The following examples serve to illustrate but are not intended to limit the scope of the present invention:

Example I To a solution of 2 g. of 3-methyl-5,10-seco-5,l9-cyclo- A -androstatrien-17,8-01 in 30 cc. of anhydroustetrahydrofuran there was added 2 g. (1.5 molar equivalents) of 2-chloro-1,1,2-trifluorotriethylamine and the reaction mixture refluxed for 20 minutes, under anhydrous condiatom R (II) Hi) (1 Bl (W) In the above formulas, R has the same meaning as heretofore set forth.

tions. It was then evaporated to dryness under reduced pressure and the residue chromatographed on 100 g. of

Example II To a solution of 2.5 g. of 3-methyl-5,l0-seco-5,19- cyclo-A -androstatrien-17 3-01 in 20 cc. of anhydrous acetonitrile there was added 1.1 molar equivalents of 2- chloro-1,1,Z-trifluorotriethylamine, and the reaction mixture was then heated on the steam bath for 15 minutes. The solvent was then evaporated to dryness under vacuo and the residue chromatographed on 125 g. of neutral alumina, thus producing 3-methyl-17a-fluoro-5,l0-seeo- 5,19-cyclo-A -androstatriene, 3-methyl-17B-chl0rofluoroacetoxy-S,10-seco-5,19-cyclo-A -androstatriene and 3,176 dimethyl 5,10 seco 5,19 cyclo-18-nor- A -androstatetraene identical to those obtained in the preceding example.

By the same method, 3-ethyl-5,10-seco-5,19-cyclo- A -aI1dI'0StatI'i6l1-1713-01 and 3-vinyl5,10-seco-5,l9- cyclo-A -androstatrien-175-01 were converted respectively into 3-ethyl-l7a-fluoro-5,IO-seco-S,19-cyclo- A -androstatriene, 3-ethyl-17,8-chlorofluoroacetoxy- 5,10-sec-5,l9-cyclo*A -androstatriene and 3-ethyl- 17B methyl 5,10-seco-5,19-cyclo-18-nor-A -androstatetraene and 3-vinyl-17a-fluoro-5,10-seco-5,l9-cyclo-A -androstatriene, 3-vinyl-17fl chlorofluoroacetoxy-S,10-seco-5,19-cycl0-A -androstatriene and 3- vinyl 17,6 methyl 5,10 seco 5,19 cyclo 18-nor- A -androstatetraene.

Example III Example I was repeated but instead of heating, the reaction mixture was allowed to stand at room temperature for 3 hours, with the same results.

Example IV I II 3-propyl-5,10-seeo-5,19 cyclo- 3-propenyl-5,10-seco-5,19-cyclo- A -androstatrien-Ufl-ol.

3-ethinyl-5,10-seeo-5,19-cyclo- A -androstatrien-Ufi-ol.

4 I claim: 1. A compound of the following formula:

wherein R is selected from the group consisting of lower alkyl, lower alkenyl and lower alkinyl.

2. 3 methyl-17a-fiuoro-5,l0-seco-5,19-cyclo-A androstatriene.

3. 3 vinyl l7a-fluoro-5,1O-seco-5,19-cyclo-A androstatriene.

4. 3 ethinyl-17u-fluoro-5,l0-seco-5,19-cyclo-A androstatriene.

5. A compound of the following formula:

wherein R is selected from the group consisting of lower alkyl, lower alkenyl and lower alkinyl.

10. 3,17,B dimethyl 5,10 seco 5,19 cyclo-18-nor A -androstatetraene.

' 11. 3 vinyl 17,8 methyl 5,10 18-nor-A -androstatetraene.

12. 3 ethinyl 17B methyl 5,10 seco 5,19 cyclo- 18-nor-A -androstatetraene.

- seco 5,19 cyclo- No references cited.

LORRAINE A. WEINBERGER, Primary Examiner. A. P. HALLUIN, Assistant Examiner. 

1. A COMPOUND OF THE FOLLOWING FORMULA:
 5. A COMPOUND OF THE FOLLOWING FORMULA:
 9. A COMPOUND OF THE FOLLOWING FORMULA: 